Murine leukemias are studied both for their use in understanding basic mechanisms of neoplasia and to identify potential host factors which participate in disease resistance. Both of these avenues have been fruitful in understanding the factors which control the expression of human cancers. We are studying a genetic locus in the mouse which restricts, in vitro the replication of a class of recombinant retroviruses implicated in the induction of F-MuLV-induced erythroleukemia. This locus encodes tow allelic endogenous retroviral gp70 molecules which are differentially expressed in different mouse strains. Our immediate goal has been to determine whether this gene participates in disease resistance in vivo and to identify the cells which express these env gene products. Backcross analysis between leukemia susceptible (IRW) and resistant (DBA/2) strains revealed that progeny receiving the endogenous gp70 gene from DBA/2 mice exhibited a strong resistance to recombinant MCF virus expression in the spleen after F-MuLV inoculation and a distinct 1 to 2 month delay in the tempo of erythroleukemia development. Previous correlative studies revealed that this gp70 gene is expressed on a population of erythroid precursors present in the early murine fetal liver and are now using cell sorting techniques to characterize these cells functionally. In addition, progress is being made toward the ultimate goal of cloning these genes.